ROLE OF CYTOKINES IN EXPERIMENTAL COLITIS - RELATION TO INTESTINAL PERMEABILITY

There is now clear evidence supporting the role of cytokines in the cl inical and immunopathological manifestations of human inflammotory bow el disease. The purpose of the present study was to determine the poss ible role of a cytokine network in a rat model of trinitrobenzene sulf onic acid-induced colitis and to examine its relation to intestinal pe rmeability. After a rapid increase in the intestinal permeability of E vans blue in the colon, tumor necrosis factor-alpha increased transien tly, and interleukin-l and interleukin-6 followed thereafter. The majo rity of tumor necrosis factor-alpha- and interleukin-1-producing cells observed by immunofluorescent staining was revealed to be macrophages . Repeated injections of interleukin-l receptor antagonist led to a mo dest decrease in myeloperoxidase activity and colon weight. These find ings suggest that enhanced pro-inflammatory cytokine production from i ntestinal macrophages accompanied by increased intestinal permeability may contribute to intestinal and systemic features of trinitrobenzene sulfonic acid-induced colitis. Pharmacologic blockade of pro-inflamma tory cytokines may help reduce intestinal inflammation.